We report the first case series of ICI-associated colitis successfully treated with fecal microbiota transplantation (FMT), with reconstitution of the gut microbiome and a relative increase in the proportion of regulatory T cells (Tregs) within the colonic mucosa. These preliminary data provide evidence that modulation of the gut microbiome may abrogate ICI-associated colitis.

In two experiments, undergraduates' evaluation and use of multiple Internet sources during a science inquiry task were examined. In Experiment 1, undergraduates had the task of explaining what caused the eruption of Mt. St. Helens using the results of an Internet search. Multiple regression analyses indicated that source evaluation significantly predicted learning outcomes, with more successful learners better able to discriminate scientifically reliable from unreliable information. In Experiment 2, an instructional unit (SEEK) taught undergraduates how to evaluate the reliability of information sources. Undergraduates who used SEEK while working on an inquiry task about the Atkins low-carbohydrate diet displayed greater differentiation in their reliability judgments of information sources than a comparison group. Both groups then participated in the Mt. St. Helens task. Undergraduates in the SEEK conditions demonstrated better learning from the volcano task. The current studies indicate that the evaluation of information sources is critical to successful learning from Internet-based inquiry and amenable to improvement through instruction.

Functional genomics approaches, which use combined computational and expression-based analyses of large amounts of sequence information, are emerging as powerful tools to accelerate the comprehensive understanding of cellular metabolism in specialized tissues and whole organisms. As part of an ongoing effort to identify genes of essential oil (monoterpene) biosynthesis, we have obtained sequence information from 1,316 randomly selected cDNA clones, or expressed sequence tags (ESTs), from a peppermint (Mentha x piperita) oil gland secretory cell cDNA library. After bioinformatic selection, candidate genes putatively involved in essential oil biosynthesis and secretion have been subcloned into suitable expression vectors for functional evaluation in Escherichia coli. On the basis of published and preliminary data on the functional properties of these clones, it is estimated that the ESTs involved in essential oil metabolism represent about 25% of the described sequences. An additional 7% of the recognized genes code for proteins involved in transport processes, and a subset of these is likely involved in the secretion of essential oil terpenes from the site of synthesis to the storage cavity of the oil glands. The integrated approaches reported here represent an essential step toward the development of a metabolic map of oil glands and provide a valuable resource for defining molecular targets for the genetic engineering of essential oil formation.functional genomics ͉ isoprenoid biosynthesis ͉ monoterpene biosynthesis E ssential oil plants have been valued historically for their medicinal, culinary, and fragrance properties and include members of the genus Mentha (mint), which produce some of the most widely used essential oils (1). The essential oil of peppermint is biosynthesized and stored in specialized anatomical structures, termed peltate glandular trichomes, on leaf surfaces (2, 3). Given the commercial value of these oils, the processes involved in their biosynthesis and secretion are attractive targets for genetic engineering. The characteristic flavor and aroma components of mint oils are monoterpenes (4). However, because of the complexity of the monoterpene biosynthetic pathway and the difficulties in purifying the responsible enzymes (5), obtaining gene probes from the corresponding target proteins by classical biochemical approaches has presented a considerable challenge.The partial sequencing of anonymous cDNA clones [expressed sequence tags (ESTs)] has become a rapid and cost-effective means of gaining information about gene expression and coding capacity of Arabidopsis thaliana (6) and rice (7). In addition, a few groups have analyzed ESTs expressed in specialized tissues and organs to assist in the identification of new genes involved in specialized pathways, such as those of developing rice endosperm (8), isolated guard cells of Brassica campestris (9), wood-forming tissues of poplar (10), and immature xylem of Loblolly pine (11).Here we report on a functional genomics approach (Fig. 1A) direct...

Previous work on learning from text has demonstrated that although illustrated text can enhance comprehension, illustrations can also sometimes lead to poor learning outcomes when they are not relevant to understanding the text. This phenomenon is known as the seductive details effect. The first experiment was designed to test whether the ability to control one's attention, as measured by working memory span tasks, would influence the processing of a scientific text that contained seductive (irrelevant) images, conceptually relevant images, or no illustrations. Understanding was evaluated using both an essay response and an inference verification task. Results indicated that low working memory capacity readers are especially vulnerable to the seductive details effect. In the second experiment, this issue was explored further, using eye-tracking methodology to evaluate the reading patterns of individuals who differed in working memory capacity as they read the same seductively illustrated scientific text. Results indicated that low working memory individuals attend to seductive illustrations more often than not and, also, for a longer duration than do those individuals high in working memory capacity.

A major goal of stem-cell research is to identify conditions that reliably regulate their differentiation into specific cell types. This goal is particularly important for human stem cells if they are to be used for in vivo transplantation or as a platform for drug development. Here we describe the establishment of procedures to direct the differentiation of human embryonic stem cells and human induced pluripotent stem cells into forebrain neurons that are capable of forming synaptic connections. In addition, HEK293T cells expressing Neuroligin (NLGN) 3 and NLGN4, but not those containing autism-associated mutations, are able to induce presynaptic differentiation in human induced pluripotent stem cellderived neurons. We show that a mutant NLGN4 containing an inframe deletion is unable to localize correctly to the cell surface when overexpressed and fails to enhance synapse formation in human induced pluripotent stem cell-derived neurons. These findings establish human pluripotent stem cell-derived neurons as a viable model for the study of synaptic differentiation and function under normal and disorder-associated conditions. neural differentiation | autism spectrum disorders | synaptogenesis P revious reports have described the differentiation of human ES (hES) cells into neurons (1-6), but they have not directly explored the kinds of in vitro experiments that may be carried out using such neurons. In addition, whether human ES and induced pluripotent stem (hiPS) cell-derived neurons follow the same differentiation programs has not been extensively examined. We sought to devise a method to direct the differentiation of hES and hiPS cells to anterior forebrain fates, as many neurodevelopmental and cognitive disorders, such as autism and schizophrenia, affect forebrain function. Current methodologies are often adapted from mouse ES cell cultures and range from cocultures with a stromal cell line (7,8) to application of recombinant factors and small molecules (3)(4)(5)(9)(10)(11)(12). We show in the present study that we were able to derive forebrain neural progenitor cells (NPCs) from both hES and hiPS cell lines, and that these NPCs can subsequently differentiate into electrophysiologically functional neurons. Furthermore, we applied such hiPS cell-derived forebrain neurons in a bioassay to test the synapse-inducing ability of Neuroligins. Neuroligins comprise a small family of transmembrane synaptic-cell adhesion molecules that are known for their ability to induce artificial synapses in heterologous nonneuronal cells and to modulate synapse numbers when overexpressed in rodent neurons (13). We used this artificial synapse formation assay to compare the synaptogenic potential of two X-linked Neuroligin mutants that have been identified in rare autistic families. In sum, human neurons differentiated in vitro from human pluripotent stem cells may serve as a useful culture system to study the functions of synaptic molecules implicated in neurodevelopmental disorders.